Evolution of anti-HER2 therapies for cancer treatment

Parakh, Sagun; Gan, Hui; Parslow, Adam C.; Burvenich, Ingrid; Burgess, Antony W.; Scott, Andrew M.

doi:10.1016/j.ctrv.2017.06.005

Cited by 74 publications

(49 citation statements)

References 284 publications

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“…HER2-HER3 heterodimer and HER2 pathway. The main elements of this pathway are phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), protein kinase B homolog (AKT(PKB)), glycogen synthesis kinase (GSK), mouse double minute-2 homolog (MDM2), mammalian target of rapamycin complex-1,2 (mTORc1,2), ribosomal protein S6 kinase beta-1 (S6K1), 4E-binding protein-1 (4EBP1), growth factor receptor-bound protein-2 (GRB2), son of sevenless (SOS), retrovirus-associated DNA sequences (RAS), rapidly accelerated fibrosarcoma (RAF), MEK mitogenactivated protein kinase phosphorylates MAPK, P-phosphorylation, human epidermal growth factor receptor (HER) [44,45]. HER2 + targeting drugs such as ado-trastuzumab emtansine (T-DM1) use trastuzumab as a drugtargeting agent to deliver emtansine to the HER2 + BC cells [46].…”

Section: Current Her2 + -Targeted Therapeutic Agents and Drug Resistancementioning

confidence: 99%

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Padmanabhan

Kheraldine

Meskin

et al. 2020

Cancers

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Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

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Section: Current Her2 + -Targeted Therapeutic Agents and Drug Resistancementioning

confidence: 99%

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Padmanabhan

Kheraldine

Meskin

et al. 2020

Cancers

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“…[1][2][3][4][5][6][7] Based on the available data, it is clear that ICD can facilitate T cell responses against a wide-spectrum of differentiation, over-expressed, and mutated tumor-associated antigens (TAAs). [1][2][3][4][8][9][10][11][12][13] However, the predominance of a fraction of TAA-specific T cells in driving ICD-based immunity might be regulated by: (1) the spatiotemporal expression patterns of specific TAAs within a tumor, [14][15][16][17][18][19][20] (2) the overall coverage of various TAAs by central or peripheral tolerance, [21][22][23] (3) the overall avidity of the T cell receptor (TCR) for specific TAA, [24][25][26][27][28][29][30][31][32] and (4) the general cellular and metabolic health of effector or memory T cell fractions. [33][34][35][36][37][38] Operationally, two experimental procedures have been established over the years to identify bona fide ICD inducers in vivo.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

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“…HER2 is the most successful ADC target for solid tumors to date, and two ADC drugs targeting it have been approved: trastuzumab emtansine (T-DM1, Kadcyla™) and trastuzumab deruxtecan (DS8201a, Enhertu™). About 15% of breast cancers were found to be HER2+ [88] along with other solid tumors such as gastric cancer [89], and targeted therapy against HER2 proved efficacious using kinase inhibitors, monoclonal antibodies, and ADCs [90]. HER2 expression level in breast cancers overall are only <2-fold higher than in normal breast tissues and the normal expression level of HER2 is higher than the expression levels on cancer cells of some of other ADC targets [83], which would make HER2 an unattractive target for ADC development.…”

Section: Target Antigensmentioning

confidence: 99%

Bispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations

Shim

2020

Biomolecules

104

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The ability of monoclonal antibodies to specifically bind a target antigen and neutralize or stimulate its activity is the basis for the rapid growth and development of the therapeutic antibody field. In recent years, traditional immunoglobulin antibodies have been further engineered for better efficacy and safety, and technological developments in the field enabled the design and production of engineered antibodies capable of mediating therapeutic functions hitherto unattainable by conventional antibody formats. Representative of this newer generation of therapeutic antibody formats are bispecific antibodies and antibody–drug conjugates, each with several approved drugs and dozens more in the clinical development phase. In this review, the technological principles and challenges of bispecific antibodies and antibody–drug conjugates are discussed, with emphasis on clinically validated formats but also including recent developments in the fields, many of which are expected to significantly augment the current therapeutic arsenal against cancer and other diseases with unmet medical needs.

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Evolution of anti-HER2 therapies for cancer treatment

Cited by 74 publications

References 284 publications

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Bispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations

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